Cognitive control of behavior is of central importance in human daily life. The hallmark of voluntary control over behavior is the ability to change an action when it no longer serves the current behavioral goal. The long-term goal of this research project is the understanding of the neural mechanisms that underlie these processes. We will study response inhibition using the stop signal task, which manipulates the ability to inhibit a movement at different degrees of preparation by presenting an imperative stop signal. This paradigm has led to a detailed mechanistic understanding of the control of eye movements by the frontal and supplementary eye field (FEF, SEF). We hypothesize that these effector-specific inhibitory mechanisms are guided and controlled by more general effector-independent cognitive systems. Recent lesion and neuroimaging work has indicated that such higher-order signals might exist in a network of areas in the medial frontal cortex (MFC), inferior frontal cortex (IFC), and subthalamic nucleus (STN). Therefore, we will test this hypothesis by determining the functional organization of response inhibition signals in MFC, IFC, and STN in macaque monkeys that are trained to inhibit both eye and arm movements. Our first aim is to understand how the frontal cortex and basal ganglia circuit interact to inhibit responses and to regulate the level of responsiveness of the motor system. In our second aim, we will identify cognitive neural activity above the effector-specific level by showing that these signals are generally important across eye and arm movement inhibition. This study will determine the underlying neural basis of motor control and has relevance toward understanding neuropsychiatric disorders such as Attention Deficit Hyperactivity Disorder (ADHD) that could arise from alterations to the circuitry underlying response inhibition. Other forms of behavioral control might use similar neural mechanisms and thus, our research might lead to insights into self-control in general. PUBLIC HEALTH RELEVANCE Cognitive control of behavior is of central importance in human daily life. The hallmark of voluntary control over behavior is the ability to suppress or change an action when it no longer serves the current behavioral goal. The long-term goal of this research project is to understand the neural mechanisms underlying behavioral control. This study has relevance toward understanding neuropsychiatric disorders such as Attention Deficit Hyperactivity Disorder (ADHD) or impulsivity that could arise from alterations to the circuitry underlying response inhibition. Other forms of behavioral control might use similar neural mechanisms and thus, our research might lead to insights into self-control in general.